Genetic Analysis of Familial Developmental Dysplasia of the Hip Associated With a Heterozygous Variant in the COMP Gene: A Case Report

ABSTRACT

Background

Developmental dysplasia of the hip (DDH) is a prevalent congenital musculoskeletal disorder characterized by structural abnormalities of the hip joint. While its etiology involves genetic and environmental factors, specific genetic mechanisms remain poorly understood. Mutations in the COMP gene (COMP; OMIM: 600310), classically associated with skeletal dysplasias such as pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), are rarely linked to isolated DDH.

Methods

A 29‐year‐old male proband with familial DDH underwent clinical evaluation and radiographic imaging. Whole‐exome sequencing (WES) was performed on the proband and his parents, followed by Sanger sequencing to validate variants in affected family members. Pathogenicity was assessed using ACMG guidelines, incorporating population frequency, conservation scores (e.g., REVEL), and clinical correlation.

Results

WES identified a heterozygous missense variant (COMP c.1133A>C, p.D378A) in exon 10, co‐segregating with the DDH phenotype across three generations. Radiographic and clinical findings excluded PSACH and MED. Functional predictions (REVEL score: 0.84) and absence in population databases supported its classification as “likely pathogenic.” Additional susceptibility genes (e.g., GDF5, OMIM: 601146; TBX4, OMIM: 601719) were detected but did not explain the familial pattern.

Conclusions

The heterozygous COMP c.1133A>C variant may be a highly penetrant pathogenic contributor to familial DDH in this pedigree, suggesting autosomal dominant inheritance. This finding suggests that COMP mutations might extend beyond classical skeletal dysplasias to significantly increase DDH risk, likely interacting with other genetic or environmental factors in line with the multifactorial etiology of DDH.

The heterozygous COMP c.1133A>C variant is a highly penetrant pathogenic contributor to familial DDH in this pedigree, demonstrating autosomal dominant inheritance. This finding suggests that COMP mutations can extend beyond classical skeletal dysplasias to significantly increase DDH risk, likely interacting with other genetic or environmental factors in line with the multifactorial etiology of DDH.

Abbreviations

ACMG

American College of Medical Genetics and Genomics

AD

autosomal dominant inherited disease

CLR

calmodulin‐like repeat domain

COMP

cartilage oligomeric matrix protein

CTD

the C‐terminal domain

CTS

Carpal Tunnel Syndrome

DDH

developmental dysplasia of the hip

DR

Digital radiography

ECM

extracellular matrix

EGF

EGF‐like domain

ER

endoplasmic reticulum

MED

multiple epiphyseal dysplasia

NTD

N‐terminal domain

PSACH

pseudoachondroplasia

THA

hip arthroplasty

THA

total hip arthroplasty

1. Introduction

Developmental dysplasia of the hip (DDH) is among the most prevalent congenital deformities, exhibiting a spectrum of anatomical abnormalities in the hip joint. The condition is characterized by a shallow or underdeveloped acetabulum, which can lead to secondary deformities of the proximal femur. Mild instability often resolves spontaneously, but if left untreated, it results in irreversible hip dislocation. The pooled prevalence of DDH was 1.40%, and the prevalence of dysplasia, subluxation, and dislocation was 1.45%, 0.37%, and 0.21%, respectively. Girls have a higher risk of DDH than boys. Though the prevalence of dysplasia has decreased, there is a slight upward trend in overall DDH (Tao et al. 2023). The debilitating pain and functional limitations associated with DDH often culminate in the development of osteoarthritis of the hip joint in adulthood, indicating the need for total hip arthroplasty (THA) as a therapeutic intervention (Nunley et al. 2011; Rogers et al. 2012). Furthermore, DDH can result in severe consequences and complications that markedly diminish patients' quality of life, such as unequal leg lengths, gait abnormalities, and spinal deformities including lordosis or scoliosis (Vaquero‐Picado et al. 2019). The etiology of DDH is multifactorial, implicating both genetic and environmental factors (Kolb et al. 2016), yet the specific pathogenic genes and mechanisms remain to be elucidated (Li, Wang, et al. 2017; Feldman et al. 2014).

The COMP gene encodes the cartilage oligomeric matrix protein (COMP), a secreted protein predominantly expressed in the pericellular matrix of chondrocytes, maintaining the homeostasis of the extracellular matrix. The COMP gene is located on chromosome 19 (19p12‐13.1). Mutations in the COMP gene can lead to various skeletal dysplasias, primarily including pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) (Briggs and Wright 1993). The main clinical manifestations include short stature, joint pain, and developmental abnormalities of the skeleton and joints. Although PSACH and MED share clinical and radiological similarities with DDH, their conditions are more extensive and severe, with a clear genetic background. In the proband of this study, such severe conditions of PSACH and MED were not observed. No abnormalities were detected in the ilium, proximal femur, or ischial pubic bone, and the adjacent soft tissues were within normal limits.

This study presents a familial case of DDH associated with a heterozygous variant in the COMP gene. Utilizing whole‐exome sequencing (WES) of DDH patients and their parents, coupled with intrafamilial validation, we identified a missense mutation in the COMP gene. Our findings suggest that this mutation may be a pathogenic or susceptibility factor for DDH within the affected family.

2. Methods

2.1. Patients

A 29‐year‐old male proband with a familial history of developmental dysplasia of the hip (DDH) presented to the genetic counseling center. The pedigree spanned three generations, encompassing 11 affected individuals, including the proband's sibling. Peripheral venous blood samples were collected from 12 family members, including the proband and his parents, for subsequent genetic analysis. All participants provided written informed consent, and the study was approved by the Ethical Review Committee of Qingdao Women's and Children's Hospital (QFELL‐YJ‐2024‐77).

2.2. Whole Exome Sequencing

Genomic DNA was extracted from peripheral blood using the QIAamp DNA Blood Mini Kit (Qiagen) following the manufacturer's protocol. A whole‐exome library was constructed using the Agilent SureSelect Human All Exon V6 kit (Agilent Technologies) with a probe hybridization capture method. Sequencing was performed on the DNBSEQ‐T7 platform (BGI Genomics) with paired‐end 150 bp reads. Raw sequencing reads were aligned to the human reference genome (GenBank: GCA_000001405.14) using BWA‐MEM (v0.7.17). Variant calling was conducted using GATK (v4.2.6.1) with HaplotypeCaller, followed by annotation via ANNOVAR (2023‐06‐01). Variants were filtered based on population frequency (gnomAD < 1%), functional impact, and ACMG guidelines.

2.3. Sanger Sequencing

Specific primers flanking the COMP c.1133A>C locus were designed using Primer3 (Table S1). PCR amplification was performed in a 25 μL reaction volume containing 50 ng genomic DNA, 0.5 μM primers, and 2× Taq PCR Master Mix (Takara). Thermal cycling conditions included initial denaturation at 95°C for 5 min, followed by 35 cycles of 95°C for 30 s, 60°C for 30 s, 72°C for 30 s, and a final extension at 72°C for 5 min. PCR products were purified using the QIAquick Gel Extraction Kit (Qiagen) and sequenced on an ABI 3730xl Genetic Analyzer (Applied Biosystems). Sequence chromatograms were analyzed using CodonCode Aligner (v10.0.1) to confirm the presence of the c.1133A>C variant.

2.4. Radiographic Assessment

DR radiographs of the hip, hand, and wrist joints were obtained for the proband, his sibling brother, and his mother. For the hip joints, anteroposterior (AP) radiographs were performed with the patient in a supine position, ensuring proper alignment of the limbs. In terms of the hands and wrists, posteroanterior (PA) radiographs were acquired with the patient's hands resting flat on the imaging table and the wrists in a neutral position to optimize visualization of the carpal bones and metacarpophalangeal joints. All radiographic examinations were carried out using a digital radiography system (Primary Diagnost DR, Philips Healthcare) with standardized imaging protocols.

3. Results

A 29‐year‐old male with a possible family history of DDH presented to the genetic counseling center for consultation. Orthopedic physicians' DR radiographic examination and diagnostic results for the proband, his sibling brother, and their mother's hip joints are as follows: The proband: Bilateral acetabular dysplasia with heterogeneous femoral head density; His sibling brother: Bilateral acetabular dysplasia with flat hip configuration; His mother: Bilateral femoral head ischemic necrosis with secondary osteoarthritis is suspected (Figure 1A). His mother also exhibited signs of DDH, while his father did not display the typical phenotype of DDH. The family's medical history included 11 cases across three generations, and the proband's full sibling was also affected (Figure 2). The proband and his sibling brother both began experiencing symptoms during childhood or adolescence. Clinical diagnosis revealed that both exhibited a limp or waddling gait when walking; a significantly restricted range of motion with a clicking sound during hip abduction maneuvers; asymmetrical gluteal skin folds; and a progressively worsening course of disease, severely affecting mobility by middle age. Both individuals reached adult heights of 166 cm and 168 cm, respectively. Currently, they exhibit phenotypes consistent with hip dislocation or dysplasia, without the presence of brachydactyly, wrist joint abnormalities, and evident scoliosis or kyphosis (Figure 1B,C). Their mother, who presents with more severe symptoms (Figure 1A; Figure S1), and other affected family members share similar phenotypes, with hip pain, abnormal gait, and limping progressively worsening with age. Consequently, we hypothesized that this represents a familial form of DDH. We performed WES on the proband and his parents to explore the molecular genetic basis of the proband's condition.

FIGURE 1.

DR radiographs and body radiographs. (A) DR radiographs of the hip joints of the proband (middle), his sibling brother (left) and his mother (right). Examination results of the proband (middle figure; age 28): Bilateral acetabular dysplasia with a more pronounced shallow and flat appearance on the right side. Femoral head flattening noted, with the left femoral head exhibiting heterogeneous density. No abnormalities observed in the ilium, proximal femur, or ischial pubic bone. Adjacent soft tissues are unremarkable. Examination results of his sibling brother (left figure; age 28): Bilateral femoral heads show near‐collapse in shape. Increased bone density is noted in the weight‐bearing regions of the femoral heads. Faint cystic and band‐like areas of osteolysis are visible. Thin sclerotic rims and irregular areas of bone sclerosis are present around these regions. No evidence of fragmentation or bone debris is noted. Bilateral acetabula are shallow and flat. No abnormalities are observed in the acetabula or the ischial pubic bones. Examination results of his mother (right figure; age 55): Bilateral femoral heads show collapse in shape. Increased bone density is noted in the weight‐bearing regions of the femoral heads. Faint cystic and band‐like areas of osteolysis are visible. Thin sclerotic rims and irregular areas of bone sclerosis are present around these regions. No evidence of fragmentation or bone debris is observed. Joint cortex is rough, and joint space is narrowed. No abnormalities are observed in the ischial pubic bone. (B) DR radiograph of the hand and wrist joint of the proband. Examination results of the proband (age 28): The osseous structures of the right hand are intact, with no evidence of specific fractures or bone destruction. The trabecular bone arrangement is regular, and there is no periosteal reaction. The interphalangeal joints and metacarpophalangeal joints show good alignment, with smooth joint surfaces and normal joint spaces. The wrist joint, as visualized in the radiograph, shows no significant abnormalities. The carpal bones of the right wrist are well‐aligned, with continuous cortical bone and clear bone texture. There is no evidence of specific fractures, dislocations, or bone destruction. The soft tissues surrounding the joints show no abnormalities. A nodular high‐density shadow is observed in the soft tissue adjacent to the 3rd metacarpal and the middle phalanx of the little finger. After inquiring about the medical history, it is preliminarily determined to be trauma‐induced, and genetic factors can be ruled out. (C) Radiographs of the spine, hands, and feet of the proband's sibling brother (above figure) and mother (bottom figure). Examination results of the proband's sibling brother (above figure; age 28) and mother (bottom figure; age 55): The spine is properly aligned, with no evident scoliosis or kyphosis, and symmetrical bilateral structures. The feet are normally aligned, with no apparent deformities of the toe joints, and the skin and nails are normal. The hands are normally aligned, with no visible deformities and no visible signs of joint swelling or deformities.

FIGURE 2.

Three‐generation pedigree of the proband's family.

After obtaining informed consent, we collected peripheral venous blood samples from the proband and his parents, extracted genomic DNA, and performed targeted enrichment using a probe hybridization capture method to construct a whole‐exome library. The pathogenic potential of mutations was assessed based on population frequency, sequence conservation, amino acid change, and protein structure location. Mutations were classified according to ACMG guidelines considering the clinical phenotype. Sanger sequencing confirmed the identified mutations in the proband, parents, and 10 additional family members using PCR with specific primers (Table S1). Sequencing data showed comprehensive capture of genomic exons and high‐quality results (Table S2). The analysis identified a heterozygous variant c.1133A>C in exon 10 of the COMP gene in the proband and his mother (Figure 3).

FIGURE 3.

WES results of the c.1133A>C variant of the COMP gene in the proband.

DDH exhibits multifactorial etiology involving complex genetic‐environmental interactions, rendering monogenic mutation hy potheses incompatible with its heterogeneous origins. To systematically identify potential pathogenic variants within this family, we relaxed allele frequency filtering criteria. By compiling known DDH‐associated pathogenic genes and potential susceptibility genes (Table 1), we observed: (1) No additional variants beyond COMP c.1133A>C were detected in the proband and his mother; (2) The proband harbored MMP24 and RETSAT mutations, while the mother carried GDF5, RETSAT (OMIM: 610157), TBX4, and PAPPA2 (OMIM: 609988) variants, and the father exhibited EDEM2 (OMIM: 610844), MMP24 (OMIM: 604871), RETSAT, KANSL1 (OMIM: 612452), and BMP2K (OMIM: 618363) mutations (Supporting Information S2). Based on population genetics criteria (rare variants defined as allele frequency < 1%), SAP scores (lower scores indicating stronger functional impacts) and other norms, we prioritized COMP, GDF5, TBX4, PAPPA2, and MMP24 for further analysis. Notably, although Genome‐wide association studies (GWAS) implicate MMP24 in DDH susceptibility (Hatzikotoulas et al. 2018), the paternal MMP24 c.979+58_979+61delACCT intronic variant showed no DDH phenotype, excluding its direct pathogenicity. Maternal exonic mutations in GDF5, TBX4, and PAPPA2 (previously linked to DDH (Hatzikotoulas et al. 2018; Wang et al. 2010; Jia et al. 2012)) were absent in the proband, genetically explaining the mother's more severe phenotype. He may be accompanied by the presence of other susceptibility genes, but may not be a major factor in the development of the disease in the family.

TABLE 1.

Genes associated with DDH development.

Gene	Function	Genetic variant	References
GDF5	Encodes growth differentiation factor 5, involved in bone and joint development.	rs143384; rs143383; methylation of promoter regions	(Hatzikotoulas et al. 2018; Wen et al. 2023; Harsanyi et al. 2021)
UQCC1	Encodes a protein associated with chondrocyte differentiation and growth control.	/	(Hatzikotoulas et al. 2018)
MMP24	Encodes a matrix metalloproteinase involved in extracellular matrix breakdown.	/	(Hatzikotoulas et al. 2018)
RETSAT	Encodes retinol saturase, involved in vitamin A metabolism and limb bud development.	/	(Hatzikotoulas et al. 2018)
PDRG1	Its role in DDH is not well defined, but may be involved in bone and joint health.	/	(Hatzikotoulas et al. 2018)
CX3CR1	Encodes a chemokine receptor related to immune cell trafficking and DDH susceptibility.	microRNAs; histone modifications	(Nejadhosseinian et al. 2022)
KANSL1	Identified as a novel pathogenic gene for DDH, with specific role yet to be elucidated.	/	(Zhao et al. 2024)
BMP2K	Involved in the regulation of the BMP signaling pathway, which affects bone and cartilage development.	c.1432_1440delCAGCAGCAG; c.1440_1441insCAG	(Zhao et al. 2017)
COL1A1	Implicated in collagen type I production; mutations can affect bone and joint integrity, potentially contributing to DDH.	Three variations in promoter: T‐139C; C‐106T; C‐35T [rs113647555]	(Zhao et al. 2013)
TBX4	Defects in TBX4 may lead to incomplete skeletal development or skeletal malalignment, which can increase the risk of DDH.	rs3744448	(Wang et al. 2010)
ASPN	ASPN abnormalities affect collagen function and bone tissue stability, increasing the incidence of DDH.	D repeat polymorphism	(Shi et al. 2011)
IL6	Abnormal expression of IL6 may affect bone formation and remodeling and thus hip joint health.	/	(Kolundžić et al. 2011)
TGFB1	TGFB1 function in skeletal development is critical for bone and connective tissue health.	/	(Kolundžić et al. 2011)
PAPPA2	Abnormal PAPPA2 may lead to alterations in the IGF signaling pathway, affecting normal bone and connective tissue development and increasing the risk of DDH.	/	(Jia et al. 2012)
TENM3	In TENM3 knock‐in mice, chondroplasia and acetabular dysplasia due to anatomical malformations led to DDH.	/	(Feldman et al. 2019)

This missense mutation substitutes aspartic acid with alanine at the 378th amino acid position (p.D378A), potentially disrupting the function of COMP (Table 2). The variant was not reported in the population gene database (ACMG: PM2‐PP). The REVEL score for this site was 0.84 (> 0.75) (ACMG: PP3). In the extended family of this case, a total of 7 individuals with joint dysplasia (excluding the proband) harbored this variant (PP1‐S). According to the variant classification guidelines of the ACMG, this variant is classified as likely pathogenic (ACMG: PS + 2PP) (Richards et al. 2015; Li, Datto, et al. 2017; Li et al. 2023). Sanger sequencing confirmed the presence of the heterozygous variant c.1133A>C in the COMP gene in all DDH‐affected family members, and the variant was inherited by the proband from their mother (Figure 4). Integrating allele frequency, functional prediction scores, and clinical concordance, we conclude that the heterozygous COMP c.1133A>C variant may represent a major monogenic contributor to DDH in this family. Its high penetrance and segregation pattern suggest a central role, consistent with it potentially contributing significantly to the phenotype within the complex genetic architecture of DDH.

TABLE 2.

The proband sequencing result analysis table.

Gene name	COMP
Reference transeript	NM_000095.3
Mutation	c.1133A>C (p.D378A)
GRCh37/hg19 location	19:18898302
Gene region	Exon 10/19
Heterozygous/homozygous	Heterozygous
Variation type	Likely pathogenic
Source of genetic variation	Maternal contribution
Inheritance pattern	AD

FIGURE 4.

Sanger sequencing tests the proband, mother, father, and other family members.

Mutations in the COMP gene are typically associated with PSACH and MED. MED is characterized by short stature, joint pain, abnormal gait, short and thick fingers and toes, and early‐onset osteoarthritis. PSACH presents with more severe manifestations, including more pronounced short stature, more significant joint pain and early‐onset osteoarthritis, and a higher frequency of spinal involvement. DDH primarily affects the hip joint, manifesting as dislocation or dysplasia, with symptoms including hip pain, abnormal gait, and limping, typically diagnosed during childhood or adolescence (Zheng et al. 2024). Given the absence of typical short‐limb dwarfism, brachydactyly, and obvious spinal deformity, and the predominant clinical manifestations of hip pain, abnormal gait, and limping (Figure 1), the skeletal disorder in this family is less likely to be PSACH or MED. Instead, the clinical presentation is more consistent with DDH. This conclusion is further supported by the lack of short‐limb dwarfism and brachydactyly in the affected family members, suggesting that the genetic condition in this family is more likely DDH rather than PSACH or MED.

4. Discussion

The etiology of DDH is multifactorial, encompassing interactions among genetic, environmental, and biological factors (O'Beirne et al. 2019). Table 3 is a comprehensive overview of the factors known to influence DDH. DDH exhibits a notable familial predisposition, with a 20% to 30% incidence rate among families with a known history of the condition. Females are more commonly affected by DDH than males (Wang 2019). A retrospective analysis of 589 DDH patients revealed that the risk of DDH in subsequent siblings is 6% if one child in the family is affected. This risk escalates to 12% if one parent is affected, and to 36% if one parent is affected and has an additional affected child (Wynne‐Davies 1970). The clinical presentation of DDH is contingent upon the patient's age and the severity of the disorder. Research suggests that initiating treatment at 8 years old confers no benefit over no treatment (Thomas 2015). Therefore, DDH screening in newborns or fetuses using genetic testing or biomarker methods could substantially enhance detection rates, facilitating early diagnosis and intervention (Basit et al. 2016).

TABLE 3.

Known factors affecting DDH.

Factor	Description
Genetic predisposition	DDH has a significant familial component, with a higher incidence in families with a history of the condition. Specific genetic mutations, such as those in the COMP gene, have been associated with DDH.
Hormonal influences	The hormonal theory suggests that an imbalance between estrogen and progesterone may contribute to DDH, with progesterone potentially facilitating dislocation.
Mechanical factors	Mechanical pressures, such as those experienced in breech presentation or oligoamnios, can lead to hip dysplasia by affecting the normal development of the hip joint.
Environmental factors	Conditions such as oligoamnios and birth position can create a mechanical environment that increases the risk of DDH.
Gender	Females are more commonly affected by DDH, which may be related to hormonal differences.
Ethnicity and geographic variation	There are noticeable differences in incidence rates among different ethnicities and regions, with the highest rates observed in Caucasians, followed by Asians.
Postural factors	The position of the fetus in utero, such as with the hips in a flexed and adducted position, can contribute to the development of DDH.
Maternal factors	Maternal factors, including age, parity, and prenatal health, may play a role in the development of DDH in offspring.

In this study, we investigate the heterozygous c.1133A>C variant in the COMP gene, which induces a missense mutation (p.D378A). The COMP molecule's crystal structure comprises the N‐terminal domain (NTD), the EGF‐like domain (EGF) with T2 repeats, the T3 repeats containing eight calmodulin‐like repeat (CLR) domains, and the C‐terminal domain (CTD). The CLR region of COMP is highly conserved and contains 13 calcium‐binding domains, which are rich in aspartic acid residues, including the aspartic acid at position 378 encoded by exons 8 to 14. Approximately 90% of pathogenic variants in the COMP gene are found within the CLR domains. We propose that this familial pathogenic variant could precipitate DDH by disrupting COMP and type IX collagen transport in cartilage. The mutated COMP is unable to oligomerize properly, leading to its accumulation in the endoplasmic reticulum (ER) and subsequent ER stress‐induced unfolded protein response and cell apoptosis. Consequently, these alterations disrupt the ECM organization and adversely affect endochondral ossification and COMP secretion by chondrocytes. The variant's co‐segregation within the family suggests that it may be a familial pathogenic mutation.

Briggs et al. (2014) observed that mutations in the T38 repeat domain of exon 14 and at the Asp509 amino acid position frequently result in PSACH. Furthermore, Mabuchi et al. reported a pathogenic variant at the Asp509 site of the COMP gene (c.1527T>G, p.Glu509Asp) that is associated with PSACH symptoms (Mabuchi et al. 2003). A Chinese clinical case study reported a patient with a heterozygous mutation in exon 14 of the COMP gene (c.1527T>A), leading to a missense mutation from Asp to Glu at position 509 and exhibiting symptoms of MED. This finding indicates a loss of gene function and suggests that distinct amino acid substitutions at the same site within the COMP gene can result in either classic MED phenotypes or a spectrum of severity from MED to PSACH. Furthermore, isolated mutations at different sites may trigger PSACH, potentially explaining the phenotypic overlap observed between our proband and patients with PSACH.

Despite the established correlation between COMP gene mutations and disease phenotypes, research on COMP mutations associated with DDH is scarce. Reproducibility in DDH studies is often low, particularly in cross‐ethnic comparisons, owing to small sample sizes and the challenges of recruiting affected patients, which hinder replication efforts. Furthermore, the link between genes and DDH pathogenesis remains unclear, with no definitive gene localization identified to date.

In the context of DDH's recognized multifactorial etiology, our findings suggest the COMP c.1133A>C variant might act as a high‐impact genetic risk factor in this family. While the variant co‐segregates strongly with DDH and meets criteria for likely pathogenicity, it likely acts within a polygenic framework. The presence of additional susceptibility alleles (e.g., GDF5, TBX4) in affected individuals, though not fully explaining the pedigree, supports the notion that COMP may interact with other genetic modifiers or environmental influences to determine final phenotype severity. Thus, while our data strongly implicate COMP c.1133A>C in this pedigree, its role in broader DDH etiology requires further validation. Future studies in larger cohorts or functional validation experiments are needed to quantify the contribution of COMP variants to DDH.

Author Contributions

Shuo Li, Yan Miao, Jiashan Li, and Siying Liang were responsible for the conceptualization, formal analysis, resources, software, and visualization of this article. Yan Miao, Jiashan Li, and Siying Liang were responsible for the investigation and methodology of this article. Siying Liang and Yan Miao were responsible for the writing of the original draft, writing of the review and editing, data curation, validation, project administration, and supervision of this article. All authors read and approved the final manuscript.

Ethics Statement

This study was approved by the Ethical Review Committee of Qingdao Women's and Children's Hospital, Shandong Province, China (QFELL‐YJ‐2024‐77).

Consent

Written informed consent was obtained from the patient for the publication of the details of this case.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Data S1.

Miao, Y. , Li J., Liang S., and Li S.. 2025. “Genetic Analysis of Familial Developmental Dysplasia of the Hip Associated With a Heterozygous Variant in the COMP Gene: A Case Report.” Molecular Genetics & Genomic Medicine 13, no. 9: e70135. 10.1002/mgg3.70135.

Data Availability Statement

All data generated or analyzed in this study are included in the published article. The raw sequence data reported in this paper have been deposited in the Genome Sequence Archive in National Genomics Data Center, China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences (GSA‐Human: HRA008752) that are publicly accessible at https://ngdc.cncb.ac.cn/gsa‐human.